The first pharmacophore model for potent G protein-coupled receptor 119 agonist

Xiaoyun Zhu; Dandan Huang; Xiaobu Lan; Chunlei Tang; Yan Zhu; Jing Han; Wenlong Huang; Hai Qian

doi:10.1016/j.ejmech.2011.04.014

The first pharmacophore model for potent G protein-coupled receptor 119 agonist

Eur J Med Chem. 2011 Jul;46(7):2901-7. doi: 10.1016/j.ejmech.2011.04.014. Epub 2011 Apr 13.

Authors

Xiaoyun Zhu¹, Dandan Huang, Xiaobu Lan, Chunlei Tang, Yan Zhu, Jing Han, Wenlong Huang, Hai Qian

Affiliation

¹ Centre of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, Jiangsu 210009, China.

PMID: 21524831
DOI: 10.1016/j.ejmech.2011.04.014

Abstract

G protein-coupled receptor 119 (GPR119) has emerged as arguably one of the most exciting targets for the treatment of type 2 diabetes mellitus in the new millennium. Pharmacophore models were developed by using Discovery Studio V2.1 with a training set of 24 GPR119 agonists. The best hypothesis consisting of five features, namely, two hydrogen bond acceptors and three hydrophobic features, has a correlation coefficient of 0.969, cost difference of 62.68, RMS of 0.653, and configuration cost of 15.24, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of the 25 known GPR119 agonists in our test set with a correlation coefficient of 0.933.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Discovery
High-Throughput Screening Assays
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Hypoglycemic Agents / chemistry*
Molecular Docking Simulation*
Receptors, G-Protein-Coupled / agonists*
Receptors, G-Protein-Coupled / chemistry
Small Molecule Libraries / chemistry*
Structure-Activity Relationship
User-Computer Interface

Substances

GPR119 protein, human
Hypoglycemic Agents
Receptors, G-Protein-Coupled
Small Molecule Libraries